Coronary heart disease (CHD) accounts for more deaths annually than any other disease, including all forms of cancer combined. Observational epidemiologic studies have established that the higher the total plasma cholesterol and low density lipoprotein cholesterol (LDL-C) levels, the greater the risk that CHD will develop.
LDL is spherical with a mass of approximately 2.5-3.0.times.10.sup.6 Daltons and a diameter of approximately 21-23 nanometers. Each LDL particle contains approximately 1500 molecules of cholesteryl ester in an oily core that is shielded from aqueous plasma by a hydrophilic coat composed of approximately 800 molecules of phospholipids, 500 molecules of unesterified cholesterol, and a 510,000-dalton protein called apoprotein B-100 or Apo B.
Total plasma cholesterol and LDL-C levels may be reduced by diets, drugs and selective removal of low density lipoproteins from the blood. However, most drugs have potentially severe side effects. More specifically, drugs that decrease cholesterol synthesis may cause serious liver injury, cataracts and fetal abnormalities. Moreover, in familial hypercholesterolemia, homozygous individuals and many heterozygotes are resistant to drug therapy.
The direct removal of a patients' blood plasma with high LDL content, removal of LDL by plasmapheresis and replacement with a low-LDL or LDL-free fluid has been shown to be effective in lowering the plasma concentration of cholesterol and low density lipoproteins. However, although plasmapheresis is a largely successful therapy, it is a nonspecific technique which is extremely expensive, primarily because the replacement fluid must be a plasma fraction.
Two affinity-column adsorption methods, one using a polyanion (heparin/agarose or dextran sulfate) and the other using anti-LDL antibodies bound to agarose, have been evaluated experimentally to selectively remove LDL. With these systems, plasma replacement is unnecessary but a pair of columns containing the affinity ligand is generally used to obviate the limited capacity of these systems, rendering these techniques difficult and expensive to make and to operate.